Quiet slot scanning

ABSTRACT

Decoupling of multiple resonances in a nuclear magnetic resonance analysis is provided by subjecting the sample to radio frequency decoupling energy centered about an RF sample irradiating frequency f1. The radio frequency decoupling energy defines a quite slot characterized by the absence of decoupling energy and which is symmetrical about the frequency f1. As sample scanning occurs, the slot progresses through the spectrum thereof enabling observance of an N.M.R. resonance substantially free from spin-coupling.

United States Patent 1 Mar. 7, 1972 Parker [54] QUIET SLOT SCANNING [72]lnventor: Leslie Kearton Parker, High Wycombe,

England [73] Assignee: Perkin-Elmer Limited, Beaconsfield,

Buckinghamshire, England [22] Filed: May 26, 1970 [21] Appl.No.: 41,695

Related US. Application Data [63] Continuation of Ser. No. 732,697, May28, 1968,

OTHER PUBLICATIONS R. Kaiser-Double Resonance Techniques for theElimination of Proton Spin-Spin Splitting in High-Resolution PMRSpectra- Rev. of Sci. Instr.-- 3 l(9)- 9/60 pp. 963- 965.

R. Emst- Nuclear Magnetic Double Resonance with an Incoherent Radio-Frequency Field- Journal of Chem. Phys.- 45(l0)- 11/15/66 pp. 3845- 3861E. B. Baker et al., Two Synthesizer Nuclear Spin DecouplinglNDORSpectroscopy- Rev. of Sci. Instr.- 34(3)- 3/63 pp. 243- 246.

Primary Examiner-Michael .l. Lynch Attorney-Edward R. Hyde, Jr.

abandoned.

[57] ABSTRACT [52] U.S.Cl. ..324/0.5R 51 1m. 0...... ..Gln 27/78Decoupling of P E P resonances a nuclear 8 581 Field ofSearch ..324/0.5Yemen analys's Pm"lded by Sublwmg SamPle radio frequency decouplingenergy centered about an RF sample irradiating frequency f The radiofrequency decoupling [56] References Clted energy defines a quite slotcharacterized by the absence of UNITED STATES PATENTS decoupling energyand which is symmetrical about the frequency f,. As sample scanningoccurs, the slot progresses 3,068,399 12/1962 Bloch ..324/0.5 throughthe Spectrum th f enabling observance f an M N.M.R. resonancesubstantially free from spin-coupling.

6 Claims, 3 Drawing Figures F Bloc/(1,416 1 l A 05c. I g I i I 4 Iwad/7M #2 I E fbWfK I IVIMK l 056mm I L I F "i I --11 C w/Wl mm I M55174m 3 1 6M 12 A/ v i 13 '9 50mm c f 15; fig; mm V 74" lgao. mom/71R I 4W fi s? '76 flu: I i Bl .705. 5 [8 L Bl/FFEA r 4/12,- i z dfiA I//,4RIIfl/l/C f mama" l l I 1 6 7 i I A7754" N.M.R. I l 0470/? PROBE e 9i R5014? l arc/11mm l\ B l L l 1 .j-QUIETSILOT SCANNING This is acontinuation of application Ser. No. 732,697, filed May 28, 1968,now-abandoned.

This invention relates to N.M.R. (Nuclear Magnetic Resonance)spectroscopy and in particular to a: method of and apparatus fordecoupling spin-coupled gyromagnetic nuclei.

Gyromagnetic nuclei .in adjacent chemical ,groups of a molecule may bespin coupled so i as to .give"rise ='to multiple resonances ormultipletsin the-observed spectrum of the coupled groups. :Although:-the presence of multiplets is itself of considerable analyticalsignificance-the.interpretation of the spectrum may be. greatlyassistedby simplifying the multiplets as, far asgpossible ideally, intosingleresonances or singlets.

Multiple resonances arise from the .fact that theaffected nucleiexperience. a disturbing influence fromsmagnetic fields duetoneighboring nuclei and are thensubjected to aneffective polarizing fieldwhich. is the resultant of both thenormal N.M.R. magnetic field (Handthedisturbing magneticfields.

-Since the.neighboringnuclei-may assume a*number=o'f permittedorientationsin the "N.M.R. magnetic field' and have a finite residencetime in each of them,=there maybe setup several discrete values ofeffective polarizingfieldgiving rise to a like number of resonances. Thesimplest case is that of protons, whichhave two-permitted orientations,viz'parallel withthe polarizing field and antipara'llel, with the'result that -two spin-coupled.protonsproduce double resonances.

A known decoupling technique .consistsin subjectingthe sampleunder-analysisto the normalirradiatingRFpower (H at the.,Larmorfrequencyoftheobserved nuclei-while superimposing on it a decoupling .RF power (Hat "the Larmor frequency of thedisturbing nuclei sufficientlyintenseito"saturate" the resonances thereof, i.e., to cause in the disturbingnuclei state 'transitionsat such a high rate, compared with theirrelaxation time, that the observed nuclei will experienceineffectadisturbing field of substantiallyzero average, with the resultthat many, multiplets originally present will be greatly simplified.

Unfortunately, a chemical group .under observation may'be spin coupledto nuclei belonging to more than one neighboring group, and thisrequires a separate decoupling RF frequency for each separate coupling,with attendantcomplexity and cost of equipment and inconvenienceto theuser.

It is an object of the present invention to provide an improved methodand apparatus for decoupling spin-coupled gyromagnetic nuclei.

According to the present invention there is provided a method ofdecoupling spin-coupled gyromagnetic nuclei in N.M.R. spectroscopy andthus generate a simplified N.M.R.

signal, wherein the N.M.R. sample is subjected to the normal irradiatingRF power (IL) and in addition is subjected to a decoupling RF power (Hwhich is adapted for saturating resonances over a region of the N.M.R.spectrum while leaving substantially unaffected a middle zone or quietslot thereof. The quiet-slot extends between limits which aresubstantially equidistant from a position on the spectrum correspondingto the irradiating RF power. As the sample is scanned in either thefrequency'scan or the field scan mode, the quiet slot flanked bysaturated zones thereby progresses along the abscissa of the spectrumand enables a resonance occurring in a chemical group of the N.M.R.sample under analysis to be observed substantially free fromspin-coupling as a midpoint of the quiet slot approaches the chemicalshift at which a resonance occurs. The width of the quiet slot is chosenwith respectto'the amplitude of the decoupling RF power and theamplitude of the irradiating 'RF power for optimizing the decouplingeffect.

In accordance with another feature of the present invention, there isprovided an apparatus fordecoupling spin-coupled gyromagnetic nuclei inN.M.R. spectroscopy, comprising means for generatinga plurality ofrelatively low-frequency signals extending over a band of frequencies, acarrier suppression modulating meansformodulating with said band offrequencies an RF signal having the same frequency, f as the normalN.M.R. irradiating RF power. RF decoupling power in group of (theNJME'R. sample undernanalysis to be observed substantially *free ='fromspin-"coupling as the 'midpoint of the quiet "slot approaches 'thechemical shift at which the "resonan'ce occurs.

The apparatus-advantag'eously includes means'for adjustingthe=width"ofthelquietslot in 'either incrementalor continuouszfashion'and for'regulating theamplitudeof'the decouplingRF ipowerto'enable the spectroscopistto'optimizethe decoupling --'t=lffet:t tosuit a particular analysis without impairing the -resonancesignalof thechemicalgroup underobservation.

'J'Fhe bandzoflow frequencies isp'roduced'by means of a plurality 'ofoscillators 'having 'a 'discrete 'frequency separation 'th'erebetween,or altematively, by generating a plurality of harmonicsaup toapredetermined limit from a low-frequency source; or alternatively,byisdlatinga'convenient band of low- :frequencynoise'from the' output ofa*nois'e generator.

Where sidebantls are generated=with a frequency spacing,

'(i-.e., ladderspacing'h between merribersof the same species (thelower-'sidebands being regarded as a separate species from 'theuppersidebands'for the=purpose of identification in:thespresenbdescription=),such as in t'hecase of the first two al-=ternativesreferred=to above,-the ladder spacing-and the amplitude o'f'the'sidebandsarechosenfor providing a spill-over .of theresonance-saturating effect so that resonancesoccurring'within:thespacing areeffectivly'saturated, although they do.not coincide with either of two consecutive sidebandsdefiningsaidspacing. However, too large a "ladder spacing cannotbe'offsetby*increasedamplitude without the risk of spilling over intothe quiet 'slot and affecting the resonance signal'under'observation.

=In :the'present context,theabscissa or horizontal axis of theN.M.R.-spectrum is intended to refer *to the'axis along which thechemical s'hiftis measured. The N.M.R. spectrum may extend from aconveniently low end "corresponding to substantially unshielded nucleior nuclei-having'an even lower chemical shiftas a resultofparamagnetic'shie'lding (in contrast to diamagnetic shielding) toaconveniently high end defined, for example,byan "intema'lreference,'i.e.,a substance mixed with the sample which is 'known to produce awell defined resonance signal at a sufficiently high-chemical shift. Thechemical shift'of an observed group may then be expressed as cycles persecond or milliga'uss from the reference, according 'to whetherfrequency scan or'magnetic'fieldscan is employed.

If desired, the whole of the N.M.R. spectrum is saturated with theexception of the quiet slot, although compared with the case where onlya relatively small region is saturated greater decoupling RF power willbe required. In addition spill-over onto the 'quiet slot may provetroublesome in certain cases.

These and other objects and features of the invention will becomeapparent with reference to the following specification and drawings,wherein:

FIG. 1 is a'diagram, in block form, illustrating three alternativeembodiments of the invention.

FIGS. Zand 3 represent indicative plots, not to scale, of the probeinput signals on the N.M.R. spectrum and are intended as an aid to theunderstanding of the three embodiments of FIG. I.

The three embodiments of FIG. I differ only in the manner in which theband of low frequencies is produced. The description relating toelements 3 through 8 of FIG. 1 which will be given in describing a firstembodiment is applicable to all three and will not therefore be repeatedfor the other two embodiments. Similarly, the description relating tothe plotting of the N.M.R. probe input signals will only be given withrespect to the first embodiment of FIG. 1, other than some additionaldescription given in connection with the third embodiment to which thegraph of FIG. 3 exclusively refers. The graph of FIG. 2 althoughspecifically directed to the first embodiment is also useful inappreciating the operation of the second.

Referring now to FIG. 1, a series of blocking oscillators 1 is shown,the output of which is passed through a weighting network 2, to providesignals at spot frequencies of 20, 25, 30 and 35 c./s. of substantiallyequal amplitude. These signals are applied via the lead A, and P to amodulator means 3 and amplitude modulate through a suppressed-carriermodulator 3 a carrier frequency f, at the irradiating RF power frequency60 Mc./s. which is derived from a source 4. In a manner well known inthe art, only the first-order sideband pair due to the modulating actionof each blocking oscillator is effective, and consequently the output ofmodulator 3 is a series of upper sidebands and a series of lowersidebands starting from the contribution made to the two series by thefirst-order sideband pair due to the 20 c./s. blocking oscillator andending with the contribution of the first-order sideband pair due to the35 c./s. oscillator. The output of modulator 3, which constitutes infact the decoupling RF power, and has sufficient amplitude for resonancesaturation is coupled through buffer amplifier 5 and attenuator 6 to anN.M.R. probe 7 of the N.M.R. spectrometer. There is also coupled toprobe 7 the irradiating RF power from source 4 through an attenuator 8vFIG. 2 is an idealized diagrammatic representation of the probe inputsignals plotted on the N.M.R. spectrum wherein the vertical axis orordinate represents signal amplitude and the horizontal axis or abscissarepresents chemical shift. The N.M.R. spectrum is seen to extend betweena low-chemicalshift limit S min. and a high-chemical-shift limit S max.the latter being conveniently chosen as a datum.

The N.M.R. spectrum is scanned between limits 8, min., e.g., chemicalshift of bare proton and 8,, max., e.g., chemical shift of T.M.S.Tetramethylsilane by either sweeping the frequency of the irradiating RFpower or the polarizing magnetic field. In either case, as scanningprogresses so the position at which the irradiating RF power may beplotted on the spectrum moves in synchronism from S, min. to 8,, max.,if the conventional mode is adapted of scanning the N.M.R. spectrum fromlowto high-chemical shifts, although the reverse mode is also possible.

In FIG. 2 the irradiating RF power reaching the probe 7 from source 4has been plotted as the monochromatic RF line M for the particularinstant when the chemical shift attained is S which may be said to be somany cycles per second or so many milligauss downscan of limit 8,, max.The decoupling RF power reaching the probe 7 from modulator 3 isrepresented by lower sidebands LSB and upper sidebands USB which aresymmetrically disposed left and right respectively of the monochromaticline M because the frequency of the suppressed carrier and that of theirradiating RF power are the same. The amplitude of the decouplingsidebands is shown in FIG. 2 to be roughly one order of magnitudegreater than that of the monochromatic line M but the range available isfrom equal amplitude to three orders of magnitude greater.

The spacing on the abscissa of the spectrum between the members L1 andU1 of the first sideband pair defines the width of the quiet slot andsimilarly the spacing between L1 and L4 constitutes the width of onesaturated zone and the spacing between U1 and U4 the width of the othersaturated zone. The width of the quiet slot is in effect 40 cycles(corresponding roughly to 9.4 milligauss) and that of each saturatedzone is 20 cycles (a little over 4.7 milligauss).

It will be clearly appreciated on the basis of the foregoing descriptionthat as the position of the monochromatic line M moves along thespectrum, the lower sidebands LSB and the upper sidebands USB retaintheir spatial relationship with the monochromatic line and progress withit.

In the present embodiment the width of the quiet slot is 40 cycles persecond as already stated while the ladder spacing is 5 c. A slot ofgreater or smaller width would have been possible without altering theladder spacing by simply arranging the blocking oscillator series tostart from a frequency respectively lower (say 15 c./s.) or higher (say25 c./s.) than in the embodiment described.

It is thus clear that having selected a ladder spacing narrow enough toinsure adequate spill over effect to saturate the spectrum in betweensidebands the width of the quiet slot may be independently adjusted indiscrete increments. If the need arises for adjusting the width inincrements smaller than consideration of the spillover effect alonewould suggest, it can be easily met by reducing the frequency intervalsbetween oscillators, which carries with it the advantage of reducing thepower requirements from individual oscillators.

Attenuators 6 and 8 are intended for the purpose of suitablyproportioning irradiating and decoupling RF power.

Referring again to FIG. 1 and considering the alternative embodiment ofthe low frequency shown by framed portion B, an oscillator 9 provides alow-frequency signal of 5 c./s. from which there is derived through aharmonic generator [0 a plurality of harmonics up to the 60th harmonicwhich is applied to modulator 3 via lines B, and P for modulating the 60Mc./s. signal from unit 4. The signal coupled to probe 7 throughattenuator 6 will comprise lower sidebands and upper sidebands, the twosideband species being symmetrically disposed either side of theposition on the abscissa of the spectrum that corresponds to the 60Mc./s. suppressed carrier, as in the case of the first embodiment. Apartfrom the greater number of sidebands involved and the smaller width ofthe quiet slot, the FIG. 2 graph is generally applicable to the presentembodiment. Each sideband species extends 300 c./s. with a 5 c./s.ladder spacing. The width of the quiet slot is twice the originallow-frequency signal, i.e., it is 10 c./s. Although this embodiment doesnot readily permit independence between quiet slot width and ladderspacing, this can be tolerated in all those cases where decoupling isnot unduly critical and would constitute a limitation quite compatiblewith a relatively inexpensive instrument.

A third embodiment of the low-frequency generator included within theframed segment c comprises a white noise generator 11 which is filteredby a filter 12 to provide a 300 c./s. white noise band extending from9.7 kc./s. to 10 kc./s. This band modulates the output of a l0 kc./s.oscillator 13 through a suppressed carrier modulator 14. The output ofthe modulator 14, which comprises a 0 to 300 c./s. lower sideband and a19.7 to 20 kc./s. upper sideband, is passed through a low-pass filter 15to yield the 0 to 300 c./s. lower sideband only. The latter output iscoupled via lines C, and P to modulator 3, modulating the 60 Mc./s.signal from source 4.

Without further provision the composite signal reaching the probe 7would be represented on the abscissa of the spectrum by the 60 Mc./s.monochromatic line flanked without intervening spacing by a continuousupper sideband 300 c./s. wide and a continuous lower sideband also 300c./s. wide. In other words, the quiet slot would have zero width. Acircuit means indicated as 16 is provided for adjustably increasing thefrequency of the 10 kc./s. oscillator 13 in the range 0-50 c./s. Thisprovides adjustment of the width of the quiet slot continuously in therange 0-100 c./s.

FIG. 3 is a representation of the probe input signals at chemical shiftS, upon an N.M.R. spectrum extending between limits 8,, min. and 8,,max. M is the 60 Mc./s. monochromatic line as in FIG. 2, LSB is thecontinuous lower sideband and USB the continuous upper sideband, eachsideband representing in effect a band of RF decoupling power extendingover 300 c./s. of the spectrum (or the equivalent in milligauss in thecase of field scan). The quiet slot is the space between the sidebands.In this embodiment the width of the quiet slot is not only independentof ladder spacing but it is also continuously adjustable. Furthermore,the effectiveness of the decoupling power is governed only by amplitude.

I claim:

1. In a nuclear magnetic resonance scanning spectrometer adapted foranalyzing a sample by subjecting the sample to an irradiating radiofrequency field and to a relatively intense magnetic field, anarrangement for decoupling spin coupled gyromagnetic nuclei comprising:

means providing irradiating radio frequency signals tuneable over afrequency range,

a suppressed carrier amplitude modulator for providing a suppressedcarrier output having a lower sideband of electromagnetic energy and anupper sideband of electromagnetic energy,

means for applying simultaneously to said modulator said irradiatingradio frequency signals to supply a carrier frequency signal and amodulating input signal exhibiting a plurality of modulatingfrequencies,

means for deriving from said modulator a modulated signal including alower sideband of electromagnetic energy extending continuouslythroughout said lower sideband and an upper sideband of electromagneticenergy extending continuously throughout said upper sideband with saidupper and lower sidebands being separated by a predetermined frequencyband that defines a quiet slot characterized by the absence of a carriersignal and modulation components,

means for tuning said irradiating radio frequency signal to move saidsignal and slot throughout a frequency spectrum, and

means for applying said modulated signal and said irradiating radiofrequency signal to said sample.

2. The apparatus as claimed in claim 1 wherein said modulating inputsignal means is adapted for altering the frequency separation betweenupper and lower sidebands.

3. The apparatus as claimed in claim 2 wherein the modulating means isadapted for altering the frequency separation in discrete increments offrequency.

4. The apparatus as claimed in claim 1 wherein said modulating inputsignal means is adapted for continuously altering the frequencyseparation between upper and lower sidebands.

5. The apparatus as claimed in claim 3 wherein said modulating inputsignal means comprises a plurality of oscillators which provide saidplurality of input signals extending over a predetermined range offrequencies in equal frequency increments and a bandwidth of saidfrequency band is adjustable by selecting an oscillator providing adesired lowest frequency.

6. The apparatus as claimed in claim 1, wherein said modulating signalinput means comprise a low-frequency source and means for generating aplurality of harmonics of the low frequency covering a band of lowfrequencies in relatively small frequency increments.

1. In a nuclear magnetic resonance scanning spectrometer adapted foranalyzing a sample by subjecting the sample to an irradiating radiofrequency field and to a relatively intense magnetic field, anarrangement for decoupling spin coupled gyromagnetic nuclei comprising:means providing irradiating radio frequency signals tuneable over afrequency range, a suppressed carrier amplitude modulator for providinga suppressed carrier output having a lower sideband of electromagneticenergy and an upper sideband of electromagnetic energy, means forapplying simultaneously to said modulator said irradiating radiofrequency signals to supply a carrier frequency signal and a modulatinginput signal exhibiting a plurality of modulating frequencies, means forderiving from said modulator a modulated signal including a lowersideband of electromagnetic energy exteNding continuously throughoutsaid lower sideband and an upper sideband of electromagnetic energyextending continuously throughout said upper sideband with said upperand lower sidebands being separated by a predetermined frequency bandthat defines a quiet slot characterized by the absence of a carriersignal and modulation components, means for tuning said irradiatingradio frequency signal to move said signal and slot throughout afrequency spectrum, and means for applying said modulated signal andsaid irradiating radio frequency signal to said sample.
 2. The apparatusas claimed in claim 1 wherein said modulating input signal means isadapted for altering the frequency separation between upper and lowersidebands.
 3. The apparatus as claimed in claim 2 wherein the modulatingmeans is adapted for altering the frequency separation in discreteincrements of frequency.
 4. The apparatus as claimed in claim 1 whereinsaid modulating input signal means is adapted for continuously alteringthe frequency separation between upper and lower sidebands.
 5. Theapparatus as claimed in claim 3 wherein said modulating input signalmeans comprises a plurality of oscillators which provide said pluralityof input signals extending over a predetermined range of frequencies inequal frequency increments and a bandwidth of said frequency band isadjustable by selecting an oscillator providing a desired lowestfrequency.
 6. The apparatus as claimed in claim 1, wherein saidmodulating signal input means comprise a low-frequency source and meansfor generating a plurality of harmonics of the low frequency covering aband of low frequencies in relatively small frequency increments.